Foscarnet

Background

• Inhibits DNA polymerase in human herpesviruses
• Indications: CMV after hematopoietic stem cell transplantation, CMV after solid organ transplantation, Cytomegalovirus, Herpes simplex virus, Herpesviridae, Post-transplant acute limbic encephalitis

Spectrum of Activity

• Active against all human herpesviruses

Mechanism of Action

• Acts as a pyrophosphate analogue that competitively and reversibly inhibits herpesvirus DNA polymerase, causing premature chain termination of DNA

Pharmacokinetics and Pharmacodynamics

• CSF penetration 66% of serum levels

Dosing

Adult Dosing

• CMV esophagitis and CMV colitis: 60 mg/kg/dose every 8 hours or 90 mg/kg/dose every 12 hours
• CMV retinitis: induction with 60 mg/kg/dose every 8 hours or 90 mg/kg/dose every 12 hours, for 14 to 21 days, followed by maintenance with 90 to 120 mg/kg/dose once daily for 3 to 6 months or longer
• Acyclovir-resistant mucocutaneous herpes simplex: 40 mg/kg/dose every 8 to 12 hours

Pediatric Dosing

• Induction: foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h
• Maintenance: foscarnet 90 to 120 mg/kg IV q24h

Administration

• Infusion rate not to exceed 1 mg/kg/min, with adult doses of 60 mg/kg typically infused over 1 hour, and doses of 90 to 120 mg/kg infused over 2 hours

Safety

Adverse Events

• Most common AEs include infusion-related nausea, electrolyte abnormalities, and acute kidney injury
  • Renal tubular nephrotoxicity is common, dose-dependent, and usually reversible if drug is stopped early
  • Crystal glomerular nephropathy also occurs
  • Electrolyte abnormalities, including hypocalcemia, hypophosphatemia, hyperphosphatemia, hypomagnesemia, and hypokalemia
  • Nausea is very common, and can be debilitating
    • Minimize with concurrent IV and oral hydration, antiemetics, and slowing the infusion rate1
• Other AEs include:
  • Seizure, usually in patients with concurrent CNS pathology
  • Genital ulcers, which slowly heal once the drug is stopped
  • Anemia
  • Nephrogenic diabetes insipidus

Monitoring

• Close monitoring of electrolytes and creatinine is required